A variety of studies have demonstrated that the behavioral effects of psychoactive drugs vary markedly during ontogeny. There has been a trend in this ontogenic work to test developing rats only up to the conventional age of weaning. Recent studies in my laboratory and others have illustrated, however, that the peri-adolescent rat differs markedly in its behavior and in its sensitivity to psychopharmacological agents when compared with younger or older animals. Animals of this age show an attenuated behavioral response to drugs that increase (amphetamine, apomorphine, clonidine) and an accentuated behavioral response to at least one drug that decreases (haloperidol), the functional activity of the catecholamine systems. However, there is a dearth of information on the behavioral responsiveness to other drugs when administered at this age and of the possible mechanisms of this altered psychopharmacological response in peri-adolescent animals. The research outlined in this proposal will examine more extensively the nature of this altered response. To begin to assess the possible hormonal role in the altered peri-adolescent drug response, ontogenetic patterns of drug responsiveness will be examined in hypophysectomized and control animal before, during and after this peri-adolescent period. In addition, since it is possible that the alterations in the behavioural responsiveness to psychoactive drugs seen in peri-adolescent animals is merely a result of some circadian shift in the baseline functional activity of the neurotransmitter target systems, diurnal cycles of the psychopharmacological responsiveness to catecholaminergic agents, regional brain levels and turnover of the catecholamines, and dopamine receptor binding will be examined in animals before, during and after this peri-adolescent period. Also, other studies outlined in this proposal will further examine the psychopharmacological responsiveness of the peri-adolescent rat by utilizing psychoactive drugs that have their primary mechanism of action on neurotransmitter systems other than the catecholamines as well as intraventricular administration of catecholaminergic agents.